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Review: Myocardial Injury in the Era of High-Sensitivity Cardiac Troponin Assays

Key findings

  • The fourth universal definition of myocardial infarction considers the phenomenon of myocardial injury as a separate, unique entity
  • Given its serious prognosis, myocardial injury warrants a thorough evaluation for its underlying precipitant
  • Both acute and chronic myocardial injury can be caused by non-cardiovascular conditions
  • To date there is no formal guideline for treating patients who have myocardial injury without infarction

Thanks to the advent of high-sensitivity cardiac troponin (cTn) assays, it's now recognized that patients can have cTn concentrations greater than the 99th percentile upper reference value without having overt myocardial ischemia. The fourth universal definition of myocardial infarction (MI), as published in Global Heart, specifies that myocardial injury is a separate entity.

Physicians should not feel falsely reassured by the absence of MI. Myocardial injury has an even worse prognosis than MI does—in one Circulation study the five-year mortality rate was 70% and the five-year rate of major cardiovascular events was 30%. What's worse, patients who have myocardial injury without evidence of infarction won't necessarily respond to conventional therapies for MI.

James L. Januzzi, Jr., MD, director of the Dennis and Marilyn Barry Fellowship in Cardiology Research at Massachusetts General Hospital, and colleagues recently reviewed the definition, epidemiology, evaluation, prognosis and treatment of myocardial injury, with special attention to differential diagnosis. Their paper appears in JAMA Cardiology.

Acute and Chronic Myocardial Injury

Myocardial injury is considered acute if the rise and/or fall of cTn concentrations exceeds the biological and/or analytical variation of the assay. There is no standard for interpreting the magnitude of the change, but if the first cTn level is greater than the 99th percentile value, then an increase of at least 50% of the 99th percentile value or a change greater than 20% relative to the baseline value can be considered acute.

Chronic myocardial injury is characterized by a cTn result greater than the 99th percentile value without a rise and/or fall over a period of serial measurements (e.g., more than eight hours).

Differential Diagnosis: Acute Myocardial Injury vs. Acute MI

The larger the rise and/or fall of cTn over a series of measurements, the higher the positive predictive value for MI. A diagnosis of acute MI requires at least one of the following forms of evidence of acute myocardial ischemia:

  • Symptoms of myocardial ischemia
  • New ischemic changes on electrocardiography
  • New ischemic regional wall-motion abnormalities on cardiac imaging
  • Acute coronary thrombus on coronary angiography

Type 2 MI (attributable to oxygen supply–demand mismatch) is particularly difficult to distinguish from myocardial injury. For one thing, the two entities can have overlapping precipitants (e.g., heart failure or sepsis). In addition, evaluating for the presence of ischemia can be challenging in some cases, such as when a patient is intubated or has atypical symptoms.

Differential Diagnosis: Evaluating Low cTn Concentrations

At lower cTn concentrations, the kind most often encountered in clinical practice, acute myocardial injury can arise from mechanisms other than ischemia. These include:

  • Mechanisms that cause increased cTn release, such as myocardial strain, inflammation, apoptosis or cell injury
  • Mechanisms that decrease cTn clearance, such as acute or chronic kidney injury

If the presentation is ambiguous, all of these mechanisms must be considered in the differential diagnosis.


No guidelines exist for treating patients who have myocardial injury without infarction. Management should focus on a thorough evaluation to identify and treat the underlying precipitant. These includes:

  • Cardiovascular causes of acute myocardial injury include pulmonary embolism, myocarditis and/or myopericarditis, aortic dissection, cardiac surgery or procedures, hypertension, arrhythmias, acute heart failure, acute valvular heart disease, takotsubo cardiomyopathy and cardiac contusions (including chest compressions)
  • Non-cardiovascular causes and/or triggers of acute myocardial injury include acute renal failure, sepsis, anemia, hypotension, hypoxia, noncardiac surgery, critical illness, rhabdomyolysis, drug-induced causes, stroke and extreme exertion
  • Cardiovascular causes of chronic myocardial injury include chronic heart failure, infiltrative cardiomyopathies, hypertrophic cardiomyopathy, stable coronary artery disease, hypertension, valvular heart disease and persistent arrhythmias
  • Non-cardiovascular causes of chronic myocardial injury include chronic renal disease, pulmonary hypertension, toxins and diabetes mellitus

Studies have examined the benefit of treating myocardial injury with various drugs to lower the risk of MI, such as pravastatin, dabigatran or canagliflozin, but most data are retrospective and/or inconclusive. Given the many possible causes of myocardial injury, it's doubtful that a single approach will be useful for all patients.

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